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Marian Goicoechea, Francisco Rivera, Juan M. López-Gómez, on behalf of all the members of the Spanish Registry of Glomerulonephritis, Increased prevalence of acute tubulointerstitial nephritis, Nephrology Dialysis Transplantation, Volume 28, Issue 1, January 2013, Pages 112–115, https://doi.org/10.1093/ndt/gfs143
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Abstract
Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury (AKI) for which early treatment improves prognosis. The recent increase in prevalence has not been reflected in the literature. The aim of our study was to analyse all native kidney biopsies performed from 1994 to 2009 and included in the Spanish Registry of Glomerulonephritis with a histological diagnosis of ATIN. We assessed the prevalence of ATIN, associated clinical syndromes and urinary sediment abnormalities. We divided the population into two groups according to age: adults (15–65 years) and elderly patients (>65 years). We collected a total of 17 680 native kidney biopsies from 120 hospitals in Spain. The overall prevalence of ATIN was 2.7%. When the analysis was restricted to patients with AKI, the prevalence increased to 12.9%. During the 16 years of follow-up, there was a significant increase in prevalence (from 3.6% in the first 4 years to 10.5% in the last 4 years), which was more marked among elderly patients (from 1.6 to 12.3%). The most common clinical manifestations were AKI, microscopic haematuria, non-nephrotic proteinuria, leucocyturia and arterial hypertension, which were more frequent in the elderly. The prevalence of ATIN has increased in recent years, especially in patients aged >65 years. This could be due to an increase in drug-associated ATIN, which would justify early renal biopsy to identify ATIN and reduce the probability of progression to chronic kidney disease. Although, our data are not able to corroborate this fact.
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Valluri A et al offer very interesting data on the registry of ATIN in Scotland, collected between January 2000 and December 2011. They also found a trend towards increasing relative incidence of ATIN (p=0.0012) and note the use of proton pump inhibitors (PPIs) in their population as one of the possible drugs associated with increased incidence of ATIN. We share the point of view that the use of PPIs in recent years has increased tremendously and we could even say that it is widespread among the population that usually take more than one drug a day. Indeed, according to the Spanish National Health System, it is estimated that 10% of the Spanish population received daily PPIs every day of 2008(1). In 2009, omeprazole was the more consumed drug in Spain and there was an increase of 9.5% in number of packages from the previous year (2,3). In addition, levels of use in Spain of this therapeutic group are much higher than those of other countries, and it is estimated that between 25 to 70% of the prescribed IPPs are not justified by clinical indication(4). However, in our experience, PPIs are not drug related so often with ATIN as antibiotics or anti-inflammatory, although they may be involved in this entity. In a retrospective Spanish study in 61 patients with biopsy-proven ATIN, the responsible drugs were antibiotics in 56%, non-steroidal inflammatory drugs in 37% and only one case was due to omeprazole (5).
REFERENCES: 1.- De Burgo Lunar C, Novo del Castillo S, Llorente D?az E, Salinero Fort MA. Estudio de prescripcion-indicacion de inhibidores de la bomba de protones. Rev Clin Esp 2006, 206:266-270 2.- Garcia del Pozo J. Estudio de utilizacion de antiulcerososos en Espa?a (2000-2008). Informacion Terapeutica del Sistema Nacional de Salud 2009; 33: 49-54. 3.-Subgrupos ATC y Principios activos de mayor consumo en el Sistema Nacional de Salud en 2009. Informacion Terapeutica del Sistema Nacional de Salud 2010; 34:89-92. 4.-Forgacs I Loganayagan A. Overprescribing proton pump inhibitors. BMJ 2008; 336:2-3. 5.-Gonzalez E, Gutierrez E, Galeano C, Chevia C, de Sequera P, Bernis C et al. Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis. Kidney Int 2008; 73:940-6.
Conflict of Interest:
None declared
Goicoechea et al. have highlighted the rising incidence of acute tubulointerstitial nephritis (ATIN) in the Spanish Registry of Glomerulonephritis 1994 - 2009 [1]. The authors speculated this could be due to an increase in drug-associated ATIN, but had no data on aetiology.
In Scotland we have recently reviewed cases of biopsy-proven ATIN over a 12 year period, between January 2000 and December 2011, presenting to two renal units (together serving 1.9 of Scotland's 5 million population).
We identified 169 cases with a histopathological diagnosis of ATIN after native renal biopsy. This represented 5.4% of the 3302 unselected renal biopsies performed. In keeping with the Spanish data, we found a trend towards increasing relative incidence (chi square test for trend 10.45) (p = 0.0012). Goicoechea et al. commented that increased, uncontrolled use of non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics may be responsible, in part, for the increasing prevalence but had not mentioned the use of proton pump inhibitors (PPIs) in their population.
Over the past 12 years, prescriptions of PPIs dispensed in the community in Scotland have increased more than two-fold, whilst the number of antibacterial and NSAID prescriptions have remained static [2]. In our study, the aetiology was thought to be drug-related in 72% of cases. PPIs were thought to be the causative agent in almost as many patients as antibiotics (23% and 27% respectively) and were more frequently implicated than NSAIDs (20%). Of note, there was a significant increase in the number of cases felt to be related to PPI prescription during 2008 - 2011, which appeared to coincide with the overall increase in ATIN during this time.
As Goicoechea et al. noted, the 1998 report of the UK MRC Glomerulonephritis Register found that in patients > 60 years, 58% of ATIN was drug-related. In those aged < 60 years the corresponding figure was 48% [3]. A 2004 review, including data from three large studies, found drug- related ATIN in 71.1% [4], a similar proportion to our cohort, suggesting the rising incidence of ATIN may well be the result of more drug-associated ATIN.
Our findings support the authors' hypothesis that the increased prevalence of ATIN may be due to an increase in drug associated causes, though establishing causation in clinical practice may be difficult, given the frequent (co-)prescription of many implicated agents.
References:
1. Goicoechea M, et al. Increased prevalence of acute tubulointerstitial nephritis. Nephrol Dial Transplant (2012) 00: 1-4.
2. http://www.isdscotland.org/Health-Topics/Prescribing-and- Medicines/Community-Dispensing/Prescription-Cost-Analysis/
3. Davison AM, Jones CH. Acute interstitial nephritis in the elderly: a report from the UK MRC Glomerulonephritis Register and a review of the literature. Nephrol Dial Transplant (1998) 13 (Suppl 7): 12-6.
4. Clarkson MR, et al. Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant (2004) 19: 2778-83.
Conflict of Interest:
None declared